RATIONALE: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors is unclear. OBJECTIVES: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (VO2peak) following rigorous adjustment for other predictors. MEASUREMENTS AND MAIN RESULTS: Data from 10 CF-centers in Australia, Europe and North America were collected retrospectively. 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation (LTx) was analyzed using Cox proportional hazards regression. In addition, phenotyping using hirarchical Ward's clustering was performed to characterize high risk subgroups. Cox regression showed-even after adjustment for sex, forced expiratory volume in 1s (%predicted), body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model-that VO2peak in %predicted, hazard ratio (HR) 0.964 [95%-CI: 0.944-0.986], peak work rate (%predicted, HR 0.969 [0.951-0.988], ventilatory equivalent for oxygen (VE/VO2peak) HR 1.085 [1.041-1.132], and carbon dioxide (VE/VCO2peak), HR 1.060 [1.007-1.115], all P<0.05) were significant predictors of death or LTx at 10 years follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high risk cluster characterized by poor lung function, nutritional status and exercise capacity. CONCLUSIONS: In conclusion, CPET provides additional prognostic information to established predictors of death/LTx in CF. High risk patients may especially benefit from regular monitoring of exercise capacity and exercise counselling.

Exercise is beneficial for patients with cystic fibrosis (CF) but long-term effects of physical activity on lung function evolution are unknown. We evaluated the longitudinal relationship between changes in habitual physical activity (HPA) and rate of decline in lung function in patients with CF.We tracked HPA using the Habitual Activity Estimation Scale, forced expiratory volume in 1 s (FEV1) and Stage I exercise tests in 212 patients with CF over a 9-year period.Adjusting for sex, baseline age and FEV1, mucoid Pseudomonas aeruginosa and CF-related diabetes, mean¡SD FEV1 % predicted decreased by 1.63¡0.08% per year (p,0.0001) while mean¡SD HPA increased by 0.28¡0.03 h?day -1 per year (p,0.0001) over the study period. A greater increase in HPA was associated with a slower rate of decline in FEV1 (r50.19, p,0.0069). Dividing subjects into ''high'' and ''low'' activity (above or below the mean rate of change of activity, respectively), a steeper rate of FEV1 decline was observed for low (-1.90% per year) compared to high (-1.39% per year) (p50.002).Increases in HPA are feasible despite progression of lung disease and are associated with a slower rate of decline in FEV1, highlighting the benefit of regular physical activity, and its positive impact on lung function in patients with CF. @ERSpublications FEV1 declines at a lesser rate in patients with cystic fibrosis who increase their activity levels

Previous studies have reported differences in muscle function and metabolism between patients with cystic fibrosis (CF) and healthy controls (HC), but it is currently unknown whether these abnormalities are specific to CF or also seen in other airway diseases. In this study, we used magnetic resonance spectroscopy (MRS) during exercise to assess muscle metabolism in CF patients. Twenty patients with CF and 20 age, gender, and habitual activity-matched HCs and a respiratory disease comparison group with primary ciliary dyskinesia (PCD; n ϭ 10) were studied.31 Phosphorus MRS ( 31 P-MRS) was used to characterize muscle bioenergetic metabolism at rest and after high-, moderate-, and low-intensity exercise. CF patients exhibited lower resting ATP/phosphocreatine (PCr) ratio and significantly higher end-exercise pH values compared with both HC and PCD patients. Both CF and PCD patients demonstrated significantly slower PCr recovery time constants after high-intensity exercise. Our results suggest that not only there are specific abnormalities of muscle metabolism in CF patients but also there is a nonspecific impact of respiratory disease on muscle function. (Pediatr Res 69: 40-45, 2011)